International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)


POSTER 32 - AN ADIPOSITY AND FASTING INSULIN QTL POSITIONED IN A 10 MB REGION OF MOUSE Chr 2

A Zuberi
Pennington Biomedical Research Center

Mahli N
Pennington Biomedical Research Center

A subcongenic mouse strain derived from the B10.LP-H3bH13b strain has been generated on the C57BL/6J (B6) genetic background.  This B6.LPa strain contains 5.2-6.5 cM of LP/J-derived DNA spanning D2Mit444 to D2Mit304.  Two main phenotypes are observed between B6.LPa and B6 mice; One, the congenic strain is resistant to the development of obesity in response to a high fat/high sucrose (HF) diet, and two, B6.LPa mice possesses significantly lower fasting insulin levels than B6 on both low fat chow and HF diets.  The genetic region containing this QTL overlaps with body weight, adiposity, hyperinsulinemia and diabetes QTL reported by others, including a QTL regulating insulin levels in mice heterozygous for the null allele of the insulin receptor gene. It is possible that polymorphism of a single gene may underlie some or all of these phenotypes.  Although the region contains many candidate genes, we describe our characterization of one polymorphic gene that is overexpressed in insulin receptor deficient mice.  This gene, Zfp106, encodes a downstream target of the insulin signaling pathway, but was initially identified as the polymorphic gene encoding the nine amino acid H3a minor histocompatibility transplantation antigen.  We have identified 26 amino acid differences between the B6 and LP-derived proteins and discovered multiple splice variants that are predicted to express polypeptides with altered functional domains.  The protein is also post-translationally processed by unknown protease(s).  Additionally, Zfp106 is polymorphic in many of the strain combinations where metabolic QTL have been mapped to this region.


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